Minimal deletion regions in lung squamous cell carcinoma: Association with abnormality of the DNA double-strand break repair genes and their applications on gene identification and prognostic biomarkers
Minimal deletion regions in lung squamous cell carcinoma: Association with abnormality of the DNA double-strand break repair genes and their applications on gene identification and prognostic biomarkers
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DOI：
10.1016/j.lungcan.2007.08.038
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发表时间：
2008-03-01
期刊：
影响因子：
5.3
通讯作者：
Wang, Yi-Ching
中科院分区：
文献类型：
--
作者：
Tseng, Ruo-Chia;Hsieh, Feng-Jen;Wang, Yi-Ching
背景：肺鳞状细胞癌(SCC)细胞经常表现出染色体不稳定的标志，如高比例等位基因丢失(FAL)。我们推测P53损伤反应基因和双链断裂(DSB)修复基因BRCA1和XRCC5的改变与高FAL患者有关。此外，染色体缺失分析能够描绘肿瘤抑制基因(TSG)的可能位置，并可以为疾病分类提供分子标记。患者和方法：为了定义最小缺失区(MDR)，我们使用了跨越先前全基因组染色体缺失研究中确定的29个区域的92个微卫星来验证36例肺鳞癌患者的最小缺失区域。结果：在肺鳞癌中发现位于2q35、3p14.1-3p14.3、3p22.2-p23、3p25.3-3p26.3、5q35.1-q35.2、9p23-p24.1、13q14.11-q14.2和17p13.1-p13.2的8个多药耐药基因。进一步检测MDR17pA(17p13.1-p13.2)候选基因Gas7和OVCA2的mRNA表达。在57%的患者中，Gas7基因的低表达提示它在肺鳞状细胞癌的发生发展中起重要作用。此外，我们还发现了一组5个微卫星(D3S1766、D4S2397、D4S2361、D13S175和D17S974)，它们可以作为肺鳞状细胞癌的预后生物标志物。此外，DSB修复相关通路中两个以上基因的改变在高FAL患者中更为明显。结论：我们的结果为监测肿瘤进展和定位克隆新的TSG提供了生物标志物。重要的是，我们的数据显示，直接证据表明，DSB修复相关通路的改变参与了肺鳞状细胞癌密集微卫星验证的基因组不稳定性。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Background: Lung squamous cell carcinoma (SCC) cells frequently exhibit markers of chromosome instability such as high fractional allelic loss (FAL). We postulated that alterations in the p53 damage responsive gene and in the double-strand break (DSB) repair genes, BRCA1 and XRCC5, are involved in patients with high FAL. In addition, chromosomal deletion analysis enables the delineation of the likely locations of tumor suppressor genes (TSG) and could provide molecular markers for disease classification.Patients and methods: To define the minimal deletion regions (MDRs), we used 92 microsatellites spanning 29 regions identified in our previous genome-wide chromosomal deletion study in 36 lung SCC patients to verify the maximal. contiguous deletion loci.Results: Eight MDRs at 2q35, 3p14.1-3p14.3, 3p22.2-p23, 3p25.3-3p26.3, 5q35.1-q35.2, 9p23-p24.1, 13q14.11-q14.2, and 17p13.1-p13.2 were found in lung SCC. The candidate genes GAS7 and OVCA2 in the MDR17pA (17p13.1-p13.2) were further examined for mRNA expression. Low expression of the GAS7 gene in 57% of patients analyzed suggested its importance in lung SCC tumorigenesis. In addition, we found a panel of five microsatellites (D3S1766, D4S2397, D4S2361, D13S175, and D17S974), which can be used as prognostic biomarkers in lung SCC. Furthermore, alteration in more than two genes in DSB repair-related pathways was more apparent in high FAL patients.Conclusions: Our results provide biomarkers that may be used for monitoring tumor progression and for positional cloning of new TSGs. Importantly, our data show direct evidence that alterations in DSB repair-related pathways are involved in the genomic instability verified by intensive microsatellites of lung SCC. (C) 2007 Elsevier Ireland Ltd. All rights reserved.